The major aim of the proposed work is to define the first specific functional and anatomical changes that occur in the brain in association with HIV infection, in cases uncomplicated by the presence of CNS opportunistic infections. Based on findings from a previous anatomical study of memory-impaired subjects, we have proposed a novel interpretation of the results of perceptual priming studies in such subjects. In brief, we obtained evidence that patterns of performance previously interpreted in terms of the subjects' limbic and neocortical damage neglected the important influence of concomitant striatal damage. Since there is evidence that HIV+ subjects frequently have damage in striatal structures, and may have additional damage in limbic and neocortical structures, the findings of our previous study are considered to have important implications for HIV+ subjects. We predict that, in the early stages, HIV- related encephalopathy will be associated with a specific pattern of behavioral deficits reflecting striatal and temporal limbic effects. Damage to the caudate nucleus in immunosuppressed HIV+ subjects is expected to produce impairment on perceptual-motor tasks, and to result in slowed perceptual identification and lexical access. In isolation, caudate damage and the subsequent perceptual-motor and lexical deficits are expected to be associated with hyperpriming on perceptual and lexical priming tasks, but normal discrimination of recently presented from novel material in recognition memory tasks. Temporal lobe limbic damage, on the other hand, is expected to result in reduced priming and reduced recognition memory. However, when both caudate and temporal limbic damage are present, the subjects are expected to exhibit poor perceptual-motor and lexical processing and poor recognition memory, but normal priming. In this instance it will be possible to show that apparently normal priming is due to augmentation of priming effects due to impaired lexical and perceptual processing of the material, combined with decrements in priming due to temporal limbic damage. Two parallel studies will be conducted to test specific hypotheses arising from this model: a neuroanatomical study in which volume losses in specific structures (as measured within the Imaging Core) will be correlated with task performance; and a functional MRI study, in which alterations in the level of activation within these structures will be correlated with behavioral and anatomical indices of encephalopathy. Seventy-five HIV+ subjects and 45 age- and education- matched controls will be examined. A series of computer-mediated, experimental tasks involving psychomotor, perceptual, and lexical processing; lexical and perceptual priming.; and explicit recall and recognition memory will be conducted. In addition, functional MR activation studies will be conducted at the time of the subjects' scheduled MRI follow-ups. The anatomical and activation studies will target the caudate nucleus (CN) and the hippocampus and adjacent parahippocampal gyrus (H/PG)